Post-transcriptional Stabilization by Interleukin-1β of Interleukin-6 mRNA Induced by c-kit Ligand and Interleukin-10 in Mouse Bone Marrow-derived Mast Cells
| Autor: | Howard R. Katz, K. Frank Austen, Jennifer M. Lu-Kuo |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_treatment
Bone Marrow Cells Biology Cycloheximide Biochemistry Mice chemistry.chemical_compound Gene expression medicine Animals Mast Cells RNA Messenger Interleukin 6 Molecular Biology Cells Cultured Stem Cell Factor Messenger RNA Interleukin-6 Interleukin Cell Biology Mast cell Molecular biology Interleukin-10 Interleukin 10 medicine.anatomical_structure Cytokine chemistry Dactinomycin biology.protein Protein Processing Post-Translational Interleukin-1 |
| Zdroj: | Journal of Biological Chemistry. 271:22169-22174 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.36.22169 |
| Popis: | We demostrate that a specific combination of cytokines elicits high levels of interleukin (IL)-6 gene expression in mast cells and define the cellular mechanisms of the exogenous cytokine action. The addition of c-kit ligand (KL) and IL-10 to IL-3-derived mouse bone marrow mast cells (BMMC) elicited an approximately 2-fold increase in steady-state IL-6 mRNA levels that peaked after 0.5 h and was followed by the release of approximately 0.2 ng of IL-6/10(6) cells by 5-7 h. The addition of IL-1beta to KL + IL-10 elicited a prolonged approximately 12-fold increase in the level of IL-6 mRNA by 3-5 h and an approximately 50-fold increase in the level of IL-6 protein released by 7 h. As determined by nuclear run-on analysis, KL + IL-10 stimulated IL-6 gene transcription within 0.5 h, and the addition of IL-1beta did not increase transcription. Instead, IL-1beta slowed by approximately 8-fold the decay of IL-6 mRNA as compared to its decay in BMMC stimulated with KL + IL-10 alone. The exposure of BMMC to cycloheximide 0.5 h before the addition of the three exogenous cytokines inhibited by approximately 50% the level of IL-6 mRNA generated but did not inhibit the effects of KL + IL-10, indicating that IL-1beta induces the synthesis of a protein that stabilizes IL-6 mRNA. The stabilization of IL-6 mRNA was inhibited by the addition of actinomycin D at 0.5 but not 3 h after BMMC were stimulated with IL-1beta in combination with KL + IL-10, suggesting that once transcribed, the stabilizing protein is long-lived. The addition of cycloheximide to BMMC after stimulation with KL + IL-10 with or without IL-1beta increased the levels of steady-state IL-6 mRNA compared to levels in cells without drug, indicating that in addition to stimulating IL-6 transcription, KL + IL-10 induces a protein factor that destabilizes IL-6 mRNA. Thus, there exists a novel Fcepsilon receptor type I-independent mechanism by which a mast cell can provide substantial amounts of IL-6 protein in response to the synergistic action of KL and IL-10 to induce IL-6 gene transcription, and IL-1beta to stabilize otherwise short-lived IL-6 transcripts. |
| Databáze: | OpenAIRE |
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